Metabolomic investigation of antihypertensive drug response. Studies of antihypertensive treatment adherence using targeted/untargeted drug screening in tertiary care hypertension patients

Hypertension is a major risk factor for several cardiovascular CV diseases. The estimated prevalence of HTN in Scotland in the adult population from 2014 to 2017 for all age groups in both sexes was 58.7%. Medication adherence is assessed using 2 different methods, either indirect or direct methods each has its own advantages and disadvantages. Non-adherence to therapy can lead to uncontrolled blood pressure (BP), deterioration in health and progression of disease state. It can also increase the cost burden on the health care system. The main aim of this study was to assess adherence by indirect methods using the self-reported Morrisby Medication Adherence Scale (MMAS-8) and direct method by untargeted and targeted drug screening in urine samples of hypertensive patients attending Glasgow Blood Pressure clinic (GBPC). Drug screening was analysed using 3 assays: First, Birmingham heartland laboratory BIR using HP LC-MS/MS. Second, Glasgow Polynomic POL using untargeted mass spectrometry data-dependent fragmentation spectra and molecular approach (based on Hydrophilic interaction liquid chromatography. Finally, Glasgow toxicology GLA using Hollow-fibre liquid-phase microextraction followed by LC-MS/MS for 10 antihypertensive drugs. 348 patients completed Morrisby questionnaire and showed that 62.1% of patients had high adherence, while 26.7% of patients had medium adherence and only 11.2 had low adherence. Despite the high adherence detected, the level of BP control was low. Only 35% of patient who reported that they were adherent had controlled SBP. 79 urine samples were sent to Birmingham heartland laboratory and the assay was able to detect complete presence of antihypertensive medication in 49 (62%) of the urine samples. Only 6 (7.6%) samples were found to be completely absent of any medication and the remaining (30.4%) detected at least one of the prescribed antihypertensive medications (partial). No drugs were detected in patients who weren’t prescribed them. 100 urine samples were sent to Glasgow Polyomics and was able to detect complete presence of antihypertensive medication in for most drugs it tested of the urine samples. 12 (12%) were completely absent of any medication. There was one false positive result. Out 173 urine samples sent to Glasgow toxicology 152 samples were tested for their prescribed drugs. Results showed only 6 (3.9%) patients weren’t detected for any medication in the sample, while 137 (89.5%) detected all the medication they were tested for and 9 (5.9%) had some their prescribed drugs detected (partial adherence). There was one false positive result. 57 samples were shared between the 3 assays for 4 antihypertensive drugs (Amlodipine, Atenolol, Losartan and Ramipril). Losartan was detected for all patient. Birmingham was the lowest method to detect amlodipine and atenolol. However, for Ramipril Birmingham identified more than the others. Glasgow Polyomics and Glasgow toxicology had high sensitivity for drugs around (80%). Glasgow Polyomics misidentified 1 patient that was prescribed metoprolol for atenolol. 79 patients were shared between Birmingham and Glasgow toxicology and were compared. Both methods agreed for most of the patients except GLA detected more for amlodipine and atenolol while Birmingham detected 1 more patient for Spironolactone. Analyses of the concentrations found by GLA doesn’t suggest those detected by GLA but not detected by BIR had lower concentrations. My study clearly shows no correlation between the Morisky score and adherence based on urine drug assays. The relationship between medication adherence and BP control is difficult to demonstrate. Adherence is an important and complex area of research that is essential to improve hypertension management and decrease the global burden of hypertension